Diagnostic and prognostic value of plasma miR-106a-5p levels in patients with acute heart failure.

BACKGROUND: It is essential to find reliable biomarkers for early diagnosis and prognosis of acute heart failure (AHF) for its mitigation. Currently, increasing attention is paid to the role of microRNAs (miRNAs/miRs) as diagnostic or prognostic markers for cardiovascular diseases. Since plasma miR-106a-5p has been observed to be downregulated in AHF, its value in the diagnosis and prognostic assessment of AHF deserves further exploration. Accordingly, this study analyzed the diagnostic and prognostic value of plasma miR-106a-5p in AHF patients. METHODS: Prospectively, this study included 127 AHF patients who met the 2021 European Society of Cardiology Guidelines and 127 control individuals. Plasma miR-106a-5p levels were determined with RT-qPCR. Spearman correlation analysis was performed to evaluate the correlation of plasma miR-106a-5p levels with NT-proBNP and hs-CRP levels in AHF patients. All AHF patients were followed up for 1 year and allocated into poor and good prognosis groups, and plasma miR-106a-5p levels were compared. The diagnostic and prognostic value of plasma miR-106a-5p for AHF was assessed with a receiver-operating characteristic curve. RESULTS: Plasma miR-106a-5p was lowly expressed in AHF patients versus controls (0.53 ± 0.26 vs. 1.09 ± 0.46) and showed significant negative correlations with NT-proBNP and hs-CRP levels. Plasma miR-106a-5p level < 0.655 could assist in AHF diagnosis. Plasma miR-106a-5p levels were markedly lower in poor-prognosis AHF patients than in good-prognosis patients. Plasma miR-106a-5p level < 0.544 could assist in predicting poor prognosis in AHF patients. CONCLUSION: Plasma miR-106a-5p is downregulated in AHF patients and could assist in diagnosis and poor prognosis prediction of AHF.

Association between urinary cobalt exposure and kidney stones in U.S. adult population: results from the National Health and Nutrition Examination Survey.

PURPOSE: Heavy metal exposure can cause impaired or reduced pathology in the kidneys, lungs, liver, and other vital organs. However, the relationship between heavy metal exposure and kidney stones has not been determined. The goal of this research was to determine the association between heavy metal exposure and kidney stones in a population of American adults in general. MATERIALS AND METHODS: We evaluated 29,201 individuals (≥20 years) from the National Health and Nutrition Examination Survey (NHANES). The association between heavy metal exposure and kidney stones was verified by multiple logistic regression and restricted cubic spline (RCS) regression. Dose-response curves were generated to analyze the relationship between heavy metal concentrations and the occurrence of kidney stones. Moreover, we used propensity score matching (PSM) to exclude the effect of confounding variables. RESULTS: After a rigorous enrollment screening process, we included 8518 participants. Logistic regression showed that urinary cadmium (U-Cd) and urinary cobalt (U-Co) concentrations were significantly different in the kidney stone group before PSM (p < 0.001). Dose-response curves revealed that the occurrence of kidney stones increased significantly with increasing U-Cd and U-Co concentrations. After adjustment for covariates, only biomarkers of U-Co were linked to the occurrence of kidney stones. When the lowest quartile was used as a reference, the 95% confidence intervals (95% CIs) for kidney stones across the other quartiles were 1.015 (0.767-1.344), 1.409 (1.059-1.875), and 2.013 (1.505-2.693) for U-Cos (p < 0.001). CONCLUSION: In the U.S. population, high U-Co levels are positively correlated with the potential risk of kidney stones.

Seasonal drought promotes citrate accumulation in citrus fruit through the CsABF3-activated CsAN1-CsPH8 pathway.

Plenty of rainfall but unevenly seasonal distribution happens regularly in southern China. Seasonal drought from summer to early autumn leads to citrus fruit acidification, but how seasonal drought regulates citrate accumulation remains unknown. Herein, we employed a set of physiological, biochemical, and molecular approaches to reveal that CsABF3 responds to seasonal drought stress and modulates citrate accumulation in citrus fruits by directly regulating CsAN1 and CsPH8. Here, we demonstrated that irreversible acidification of citrus fruits is caused by drought lasting for > 30 d during the fruit enlargement stage. We investigated the transcriptome characteristics of fruits affected by drought and corroborated the pivotal roles of a bHLH transcription factor (CsAN1) and a P3A-ATPase gene (CsPH8) in regulating citrate accumulation in response to drought. Abscisic acid (ABA)-responsive element binding factor 3 (CsABF3) was upregulated by drought in an ABA-dependent manner. CsABF3 activated CsAN1 and CsPH8 expression by directly and specifically binding to the ABA-responsive elements (ABREs) in the promoters and positively regulated citrate accumulation. Taken together, this study sheds new light on the regulatory module ABA-CsABF3-CsAN1-CsPH8 responsible for citrate accumulation under drought stress, which advances our understanding of quality formation of citrus fruit.

Novel Therapeutic Targets on the Horizon: An Analysis of Clinical Trials on Therapies for Bone Metastasis in Prostate Cancer.

In the absence of early detection and initial treatment, prostate cancer often progresses to an advanced stage, frequently spreading to the bones and significantly impacting patients' well-being and healthcare resources. Therefore, managing patients with prostate cancer that has spread to the bones often involves using bone-targeted medications like bisphosphonates and denosumab to enhance bone structure and minimize skeletal complications. Additionally, researchers are studying the tumor microenvironment and biomarkers to understand the mechanisms and potential treatment targets for bone metastases in prostate cancer. A literature search was conducted to identify clinical studies from 2013 to 2023 that focused on pain, performance status, or quality of life as primary outcomes. The analysis included details such as patient recruitment, prior palliative therapies, baseline characteristics, follow-up, and outcome reporting. The goal was to highlight the advancements and trends in bone metastasis research in prostate cancer over the past decade, with the aim of developing strategies to prevent and treat bone metastases and improve the quality of life and survival rates for prostate cancer patients.

The effect of background information and motion speed on the performance of TTC estimation.

BACKGROUND: In previous studies, most research on motion perception have been conducted under background-free condition when the stimulus moved in a plane parallel to the observer. In real-life situations, people's perception of the motion state of objects is usually done under different visual noise. Based on the occlusion paradigm, this study aimed to investigate whether different background information and motion speed affect the trend and accuracy of time-to-collision (TTC) estimation when stimuli move in a plane parallel to the observer. METHODS: Thirty five college students (mean age = 20.94, SD = 2.95, range = 18-28 years) participated in experiment 1, and used a 2 (background orientation: horizontal, vertical) × 3 (motion speed: slow, medium, fast) design to explore the effect of different line segment orientations and motion speed on TTC estimation performance; 36 college students (mean age = 20.81, SD = 2.82, range = 18-28 years) participated in experiment 2, and used a 2 (background dimension: two-dimensional background, three-dimensional background) × 3 (motion speed: slow, medium, fast) design to explore the effect of different background dimensions and motion speed on the performance of TTC estimation. The data were analyzed using SPSS 25.0. RESULTS: The results revealed that: (1) The TTC was underestimated for the slow speed condition and overestimated for the medium and fast speed conditions. (2) The highest accuracy of TTC estimation was obtained for the fast condition. (3) The TTC were overestimated for the vertical background condition and underestimated for the horizontal background condition. (4) Compared to the two-dimensional background, the TTC was overestimated in the three-dimensional background. CONCLUSIONS: Object motion speed affected the TTC estimation performance, and different background information affected the TTC estimation performance when the object moved in a plane parallel to the observer. Meanwhile, the impact of background orientation and motion speed showed significant interactions.

MicroRNA-148a-3p in pericyte-derived extracellular vesicles improves erectile function in diabetic mice by promoting cavernous neurovascular regeneration.

BACKGROUND: To investigate the regulatory role of microRNA (miR)-148a-3p in mouse corpus cavernous pericyte (MCPs)-derived extracellular vesicles (EVs) in the treatment of diabetes-induced erectile dysfunction (ED). METHODS: Mouse corpus cavernous tissue was used for MCP primary culture and EV isolation. Small-RNA sequencing analysis was performed to assess the type and content of miRs in MCPs-EVs. Four groups of mice were used: control nondiabetic mice and streptozotocin-induced diabetic mice receiving two intracavernous injections (days - 3 and 0) of phosphate buffered saline, MCPs-EVs transfected with reagent control, or MCPs-EVs transfected with a miR-148a-3p inhibitor. miR-148a-3p function in MCPs-EVs was evaluated by tube-formation assay, migration assay, TUNEL assay, intracavernous pressure, immunofluorescence staining, and Western blotting. RESULTS: We extracted EVs from MCPs, and small-RNA sequencing analysis showed miR-148a-3p enrichment in MCPs-EVs. Exogenous MCPs-EV administration effectively promoted mouse cavernous endothelial cell (MCECs) tube formation, migration, and proliferation, and reduced MCECs apoptosis under high-glucose conditions. These effects were significantly attenuated in miR-148a-3p-depleted MCPs-EVs, which were extracted after inhibiting miR-148a-3p expression in MCPs. Repetitive intracavernous injections of MCPs-EVs improved erectile function by inducing cavernous neurovascular regeneration in diabetic mice. Using online bioinformatics databases and luciferase report assays, we predicted that pyruvate dehydrogenase kinase-4 (PDK4) is a potential target gene of miR-148a-3p. CONCLUSIONS: Our findings provide new and reliable evidence that miR-148a-3p in MCPs-EVs significantly enhances cavernous neurovascular regeneration by inhibiting PDK4 expression in diabetic mice.

Frenulum Protection Technique in Disposable Circumcision Suture Device for Adult Males.

PURPOSE: To evaluate the efficacy of frenulum protection technique of the disposable circumcision suture device (DCSD) in adult males. MATERIALS AND METHODS: Atotal of 53 adult males were diagnosed with redundant prepuce and underwent circumcision with DCSD using frenulum protection technique. The main preoperative and postoperative measure of the length of penile frenulum was evaluated. Other data such as edema rate, intraoperative blood loss, operation time, postoperative pain, staple falling off time, incision infection rate, and evaluation of satisfaction rate with penis appearance were documented in the study. RESULTS: There was no significant difference in preoperative and postoperative frenulum length for each patient. The mean length of the penile frenulum before and after surgery was 2.25 ± 0.36 cm and 2.23 ± 0.39 cm, respectively (p = .31). The rate of frenulum length preservation was 100%. All the patients had no excessive resection of the frenulum and no serious complication happened after surgery. The satisfaction rate of postoperative penis appearance from patients' evaluation was 98.1% (52/53). CONCLUSION: The frenulum protection technique was simple and operable, which could help the operator to accurately identify the most distal position of the frenulum and retain a sufficient length of frenulum during DCSD circumcision.

EEG and ECG-Based Multi-Sensor Fusion Computing for Real-Time Fatigue Driving Recognition Based on Feedback Mechanism.

A variety of technologies that could enhance driving safety are being actively explored, with the aim of reducing traffic accidents by accurately recognizing the driver's state. In this field, three mainstream detection methods have been widely applied, namely visual monitoring, physiological indicator monitoring and vehicle behavior analysis. In order to achieve more accurate driver state recognition, we adopted a multi-sensor fusion approach. We monitored driver physiological signals, electroencephalogram (EEG) signals and electrocardiogram (ECG) signals to determine fatigue state, while an in-vehicle camera observed driver behavior and provided more information for driver state assessment. In addition, an outside camera was used to monitor vehicle position to determine whether there were any driving deviations due to distraction or fatigue. After a series of experimental validations, our research results showed that our multi-sensor approach exhibited good performance for driver state recognition. This study could provide a solid foundation and development direction for future in-depth driver state recognition research, which is expected to further improve road safety.

ECG Multi-Emotion Recognition Based on Heart Rate Variability Signal Features Mining.

Heart rate variability (HRV) serves as a significant physiological measure that mirrors the regulatory capacity of the cardiac autonomic nervous system. It not only indicates the extent of the autonomic nervous system's influence on heart function but also unveils the connection between emotions and psychological disorders. Currently, in the field of emotion recognition using HRV, most methods focus on feature extraction through the comprehensive analysis of signal characteristics; however, these methods lack in-depth analysis of the local features in the HRV signal and cannot fully utilize the information of the HRV signal. Therefore, we propose the HRV Emotion Recognition (HER) method, utilizing the amplitude level quantization (ALQ) technique for feature extraction. First, we employ the emotion quantification analysis (EQA) technique to impartially assess the semantic resemblance of emotions within the domain of emotional arousal. Then, we use the ALQ method to extract rich local information features by analyzing the local information in each frequency range of the HRV signal. Finally, the extracted features are classified using a logistic regression (LR) classification algorithm, which can achieve efficient and accurate emotion recognition. According to the experiment findings, the approach surpasses existing techniques in emotion recognition accuracy, achieving an average accuracy rate of 84.3%. Therefore, the HER method proposed in this paper can effectively utilize the local features in HRV signals to achieve efficient and accurate emotion recognition. This will provide strong support for emotion research in psychology, medicine, and other fields.

Glabridin Functions as a Quorum Sensing Inhibitor to Inhibit Biofilm Formation and Swarming Motility of Multidrug-Resistant Acinetobacter baumannii.

Objective: Acinetobacter baumannii is a hazardous bacterium that causes hospital-acquired nosocomial infections, and the advent of multidrug-resistant A. baumannii (MDR-AB) strains is concerning. Novel antibacterial therapeutic strategies must be developed. The biological effects of glabridin on MDR-AB were investigated in this study. Methods: The minimum inhibitory concentrations (MICs) of glabridin against eight clinical MDR-AB strains were determined using the broth microdilution technique. Crystal violet staining was used to assess biofilm development, which has significant contribution to bacterial resistance. Swarming motility was measured according to surface growth zone of MDR-AB on LB agar medium. qRT-PCR was used to evaluate the expression of quorum sensing genes abaI and abaR. Glabridin and routinely used therapeutic antimicrobial agents were tested for synergistic action using the checkerboard method. Results: According to our findings, glabridin suppressed MDR-AB growth at high doses (512-1024 µg/mL). The 1/4 MIC of glabridin significantly decreased MDR-AB biofilm formation by 19.98% (P < 0.05), inhibited MDR-AB motility by 44.27% (P < 0.05), whereas the 1/2 MIC of glabridin dramatically reduced MDR-AB biofilm development by 27.43% (P < 0.01), suppressed MDR-AB motility by 50.64% (P < 0.05). Mechanistically, glabridin substantially downregulated the expression of quorum sensing-related genes abaI and abaR by up to 39.12% (P < 0.001) and 25.19% (P < 0.01), respectively. However, no synergistic effect between glabridin and antibacterial drugs was found. Conclusion: Glabridin might be a quorum sensing inhibitor that inhibits MDR-AB biofilm development and swarming motility.

Comparison of population characteristics and clinical outcomes of patients with type B aortic dissection or aortic intramural hematoma underwent thoracic endovascular aortic repair: a propensity score-matched analysis.

BACKGROUNDS: Survival and aortic-related adverse events after thoracic endovascular aortic repair (TEVAR) for aortic intramural hematoma (IMH) and aortic dissection (AD) are controversial. We aimed to assess the preoperative characteristics and to evaluate TEVAR outcomes of acute type B IMH and AD. METHODS: Between June 2002 and May 2021, 83 patients with acute type B IMH and 755 patients with acute type B AD underwent TEVAR at the General Hospital of Northern Theater Command. We retrospectively analyzed data from these patients, including clinical characteristics and follow-up outcomes. RESULTS: The patients with IMH were significantly older than the ones with AD (P < 0.001). Diabetes mellitus (P = 0.035) and ischemic cerebrovascular disease (P = 0.017) were more common in the IMH group than in the AD group. The results demonstrated a less long-term aortic-related death-free survival rate in the IMH group than the AD group for all the patients (P = 0.014) and the matched patients (P = 0.027). It also presents a lower long-term overall survival rate (P = 0.047) and aortic-related event-free rate (P = 0.048) in the IMH group than in the matched patients. CONCLUSIONS: Compared with AD patients, patients with IMH who underwent TEVAR had a worse long-term outcome of aortic-related survival in all and matched patients.

Proxalutamide in metastatic castration-resistant prostate cancer: Primary analysis of a multicenter, randomized, open-label, phase 2 trial.

We aim to assess the safety and efficacy of proxalutamide, a novel androgen receptor antagonist, for men with metastatic castration-resistant prostate cancer (mCRPC) in a multicenter, randomized, open-label, phase 2 trial. In our study, the enrolled mCRPC patients were randomized to 100, 200 and 300 mg dose groups at 1:1:1. The primary efficacy endpoint was prostate-specific antigen (PSA) response rate. The secondary endpoints included objective response rate (ORR), disease control rate (DCR) and time to PSA and radiographic progression. Safety and pharmacokinetics were also assessed. Finally, there were 108 patients from 17 centers being enrolled. By week 16, there were 13 (35.1%), 12 (36.4%) and 15 (42.9%) patients with confirmed 50% or greater PSA decline in 100 mg (n = 37), 200 mg (n = 33) and 300 mg (n = 35) groups, respectively. Among the 19 patients with target lesions at study entry, three (15.8%) had a partial response and 12 (63.2%) had stable disease. The ORRs of 20.0%, 22.2%, 0% and DCRs of 80.0%, 88.9%, 60.0% were, respectively, achieved in 100, 200 and 300 mg groups. By the maximum follow-up time of 24 weeks, there were 42.6% and 10.2% of cases experiencing PSA progression and radiographic progression, respectively. Overall, adverse events (AEs) were experienced by 94.4% of patients, most of which were mild or moderate. There were 28 patients experiencing ≥grade 3 AEs. The most common AEs were fatigue (17.6%), anemia (14.8%), elevated AST (14.8%) and ALT (13.0%), decreased appetite (13.0%). These findings preliminarily showed the promising antitumor activity of proxalutamide in patients with mCRPC with a manageable safety profile. The proxalutamide dose of 200 mg daily is recommended for future phase 3 trial (Clinical trial registration no. CTR20170177).

Field-Free Magnetization Switching in a Ferromagnetic Single Layer through Multiple Inversion Asymmetry Engineering.

A simple, reliable, and self-switchable spin-orbit torque (SOT)-induced magnetization switching in a ferromagnetic single layer is needed for the development of next generation fully electrical controllable spintronic devices. In this work, field-free SOT-induced magnetization switching in a CoPt single layer is realized by broken multiple inversion symmetry through simultaneously introducing both oblique sputtering and a vertical composition gradient. A quantitative analysis indicates that multiple inversion asymmetries can produce dynamical bias fields along both z- and x-axes, leading to the observed field-free deterministic magnetization switching. Our study provides a method to accomplish fully electrical manipulation of magnetization in a ferromagnetic single layer without the external magnetic field and auxiliary heavy metal layer, enabling flexible design for future spin-orbit torque-based memory and logic devices.

Enzalutamide-resistant related lncRNA NONHSAT210528 promotes the proliferation and invasion of prostate cancer.

Background: As a new-generation androgen-receptor antagonist, enzalutamide is a first-choice drug for advanced prostate cancer (PCa) patients. However, secondary resistance to enzalutamide poses a new challenge in the treatment of cancer. Long non-coding RNA (lncRNA) regulates cell function through many levels and mechanisms, and also plays an important role in the biological behaviors of tumors. Methods: LncRNA microarrays were used to detect enzalutamide-resistant related lncRNA in Enzalutamide-resistant C4-2 (C4-2 ENZ-R) cells and corresponding parent cells. Cell Counting Kit 8, flow cytometry, and transwell assays were used to test the effect of lncRNA NONHSAT210528 on the function of PCa cells. RNA pulls down and the luciferase report gene was used to detect the competitive endogenous RNA (ceRNA) mechanism. The culture supernatant of C4-2 and C4-2b cells was transferred to the lower chamber for transwell assay of human umbilical endothelial cells (HUVECs). Results: The lncRNA microarray analysis showed that there were significant differences in the expression of many lncRNAs between the C4-2 ENZ-R and C4-2 cells. The real-time polymerase chain reaction (PCR) detection showed that the expression of lncRNA NONHSAT210528 was significantly higher in the C4-2 ENZ-R cells than the C4-2 cells. The Transwell assays showed that lncRNA NONHSAT210528 overexpression increased the invasion of the C4-2 and C4-2b cells. The cell-wound scratch and the transwell assays showed that the culture supernatant of C4-2 and C4-2b cells with overexpressed lncRNA NONHSAT210528 promoted the migration and invasion of HUVECs. Furthermore, lncRNA NONHSAT210528 regulated the expression of YOD1 dependent on miR-21. Conclusions: Enzalutamide-resistant related lncRNA NONHSAT210528 appears to promote the proliferation and invasion of PCa cells by functioning as a ceRNA and regulating the miR-21-5p/YOD1 signal pathway.

Efficacy and Safety of the Reduced Bivalirudin in Patients Undergoing Coronary Angiography or Percutaneous Coronary Intervention Stratified by Renal Function (REDUCE BOLUS): A Single-Blind, Stratified Randomized, Non-inferiority Trial.

Background: In clinical practice, some cases indicated that the loading dose of bivalirudin increased the bleeding risk, particularly in patients with renal insufficiency. Therefore, this study aimed to assess the efficacy and safety of the low-dose (80%) bolus injection of bivalirudin in patients undergoing cardiac catheterization stratified by renal function. Methods: A total of 204 individuals in the REDUCE BOLUS trial were stratified 1:1 to the estimated glomerular filtration rate (eGFR) ≥ 60 ml/min cohort or eGFR < 60 ml/min cohort, then randomized 1:1 to the reduced bolus bivalirudin group (i.e., the experimental group) or normal bolus bivalirudin group (i.e., the control group), respectively. The primary end point was to compare the differences of the area under the curve of activated clotting time (ACT) between the two groups. The secondary end points were the postoperative net adverse clinical events (NACEs) before discharge, defined as the all-cause mortality, recurrent myocardial infarction, ischemia-driven target vessel revascularization, stroke, and bleeding events. Results: Between January 3, 2020, and March 26, 2021, 204 patients undergoing coronary angiography were randomly assigned, including 102 (i.e., 51 in the control group and 51 in the experimental group) with normal eGFR and 102 (i.e., 51 control and 51 experimental) with abnormal eGFR. No difference was observed in the curve of ACT between the control group and the experimental group (0.55 ± 0.09 vs. 0.56 ± 0.08, P = 0.542 and 0.55 ± 0.06 vs. 0.57 ± 0.05, P = 0.075, respectively, for normal eGFR cohort and abnormal eGFR cohort). The one-sided 97.5% lower confidence bound for the difference in the area under the ACT curve was -0.017 and 0.0015 in eGFR ≥ 60 ml/min and eGFR<60 ml/min cohort, respectively, both above the preset non-inferiority criterion of -0.07, establishing the non-inferiority. There was no incidence of NACE and stent thrombosis before discharge in each group. Conclusion: In patients undergoing cardiac catheterization, the efficacy and safety of the reduced bolus of bivalirudin were non-inferior to the normal one, even in patients without chronic kidney disease. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT03588611].

EEG Emotion Recognition Applied to the Effect Analysis of Music on Emotion Changes in Psychological Healthcare.

Music therapy is increasingly being used to promote physical health. Emotion semantic recognition is more objective and provides direct awareness of the real emotional state based on electroencephalogram (EEG) signals. Therefore, we proposed a music therapy method to carry out emotion semantic matching between the EEG signal and music audio signal, which can improve the reliability of emotional judgments, and, furthermore, deeply mine the potential influence correlations between music and emotions. Our proposed EER model (EEG-based Emotion Recognition Model) could identify 20 types of emotions based on 32 EEG channels, and the average recognition accuracy was above 90% and 80%, respectively. Our proposed music-based emotion classification model (MEC model) could classify eight typical emotion types of music based on nine music feature combinations, and the average classification accuracy was above 90%. In addition, the semantic mapping was analyzed according to the influence of different music types on emotional changes from different perspectives based on the two models, and the results showed that the joy type of music video could improve fear, disgust, mania, and trust emotions into surprise or intimacy emotions, while the sad type of music video could reduce intimacy to the fear emotion.

Phase I clinical trial of HC-1119 soft capsule in Chinese healthy adult male subjects: Pharmacokinetics and safety of single-dose proportionality and effects of food.

BACKGROUND: Preclinical studies showed that HC-1119, a deuterated version of enzalutamide, could competitively inhibit androgen binding to androgen receptor by blocking the transmission of androgen receptor signaling pathway as enzalutamide, inducing apoptosis of prostate cancer cells and reducing the proliferation of prostate cancer cells. Animal pharmacokinetic studies also show that deuterization of enzalutamide as HC-1119 could retain the basic properties of mother drug, increases the stability of compounds to metabolic enzymes and the drug exposure in vivo, prolong the half-life and reduce the production of metabolites, which may lead to a better efficacy and safety of HC-1119 compared with enzalutamide. METHODS: To evaluate the pharmacokinetics and safety of HC-1119 and the effects of food on pharmacokinetics in healthy adult Chinese men after single-dose administration of HC-1119. A total of 47 Chinese healthy adult male subjects received HC-1119 soft capsule at a single oral dose of 40, 80, or 160 mg followed on fasting or 160 mg after high-fat meal respectively. HC-1119 prototype and its metabolites M1 and M2 in plasma were collected individually in a total 23 time points. Pharmacokinetics were determined by sensitive LC/MS/MS for dose-proportionality study. RESULTS: In subjects taking HC-1119 soft capsules on fasting, Cmax of HC-1119 prototype increased dose-dependently. Either Cmax and AUC0-∞ of M1 or Cmax of M2 showed statistically significant difference. Dose-proportionality evaluation showed linear pharmacokinetic characteristics in Cmax of HC-1119 prototype, Cmax and AUC0-∞ of M2 in dose range of 40-160 mg. Cmax of HC-1119 was significantly different between the two groups as 160 mg HC-1119 on fasting or after a high-fat diet respectively, while the other parameter were not. HC-1119 and its metabolites M1 and M2 showed a linear dynamic trend. CONCLUSIONS: HC-1119 is expected to have lower clinical dose than the similar drug enzalutamide. The absorption of HC-1119 and the main pharmacokinetic parameters of HC-1119 and its metabolites M1 and M2 were not affected by high-fat diet. The clinical application of HC-1119 soft capsule in the later stage can be recommended for both fasting and postprandial. The safety and tolerance were good in this population.

A lncRNA-immune checkpoint-related gene signature predicts metastasis-free survival in prostate adenocarcinoma.

Background: The 5-year overall survival rate in metastatic prostate adenocarcinoma (PRAD) is extremely low. Genomic studies of PRAD have improved our understanding of disease biology. However, the role of immune checkpoint genes (ICGs) in PRAD remains unclear. Methods: Univariate and multivariate analyses were used to analyze genes associated with metastasis-free survival (MFS) in The Cancer Genome Atlas (TCGA)-PRAD dataset. The expressions of ADORA2A and TNFRSF18 were detected via immunohistochemical assay and real-time fluorescence quantitative PCR (RT-PCR) assay in our in-house cohort. The expression of long non-coding RNAs (lncRNAs) AL139287.1, SLC9A3-AS1, and SNHG12 were detected via RT-PCR assay in our in-house cohort. Stepwise regression, Cox regression, and nomogram analyses were used to evaluate the prognostic role of these genes in both the TCGA dataset and in-house cohort. The "pRRophetic" R package was used to evaluate drug sensitivity in the TCGA cohort according to the gene mRNA expression level. Results: In our study, univariate and multivariate analyses revealed that the mRNA expressions of two ICGs, ADORA2A and TNFRSF18, were independent factors affecting MFS in PRAD patients. A prognostic 2-ICG model predicted the MFS of PRAD patients with medium-to-high accuracy in the TCGA dataset and in-house cohort. The expressions of AL139287.1, SLC9A3-AS1, and SNHG12 were correlated with ADORA2A and TNFRSF18. A prognostic lncRNA-ICG model predicted the MFS of PRAD patients with medium-to-high accuracy in the TCGA dataset and in-house cohort. In addition, correlation analyses between the sensitivity of doxorubicin, erlotinib, gemcitabine, or vinorelbine and AL139287.1, SLC9A3-AS1, SNHG12, ADORA2A, and TNFRSF18 were conducted. Conclusions: Our results provide new targets for predicting tumor metastasis in PRAD and treating patients with metastatic PRAD.

Skin and soft tissue infection caused by Cysteiniphilum litorale in an immunocompetent patient: A case report.

Cysteiniphilum litorale is a Gram-negative coccobacillus first isolated from the seawater of Wailingding Island near the estuary of Pearl River in southern China. This organism was previously not considered to cause disease in animals or humans. We report a case of a 19-year-old female patient infected with abscess caused by C. litorale in the middle digit of her right hand after minor trauma during the handling of estuarine shrimps at home. C. litorale was cultured from the wound exudate of the patient and identified by 16S rRNA gene sequencing. Whether C. litorale may be transmitted to humans via other channels requires further exploration.